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- Clinical Introduction
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1. Frontotemporal dementia
- Prof. Bruce Miller
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2. Parkinson disease
- Prof. Stanley Fahn
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3. Atypical parkinsonian syndromes
- Dr. David Burn
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4. Huntington's disease
- Prof. Roger Barker
- Neuroimaging
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5. Molecular brain imaging (PET) in diseases with dementia
- Prof. Karl Herholz
- Pathology, Genetic and Molecular Aspects (1)
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6. A molecular understanding of Alzheimer's disease
- Prof. John Hardy
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7. Neuropathology of neurodegenerative disorders
- Prof. Jillian Kril
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9. Ubiquitination and Alzheimer related disorders
- Prof. John Mayer
- Pathology, Genetic and Molecular Aspects (2)
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10. The molecular biology of Huntington's disease
- Prof. David C. Rubinsztein
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11. Metals, oxidative stress and neurodegeneration
- Prof. Ashley Bush
- Latest Developments in the Field
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12. Animal models of tauopathy
- Prof. David Westaway
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13. Parkinson's disease and transplants
- Prof. Roger Barker
- Archived Lectures *These may not cover the latest advances in the field
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14. Neuropathology of neurodegenerative disorders
- Prof. Jillian Kril
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15. Motor neurone disease: molecular basis
- Prof. Kevin Talbot
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16. Alzheimer's disease (AD)
- Prof. John Hodges
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17. Frontotemporal dementia syndromes
- Prof. John Hodges
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18. Motor neurone disease: clinical aspects
- Prof. Kevin Talbot
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19. Neuro-imaging in dementia: using MRI in routine work-up
- Prof. Philip Scheltens
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20. Prion diseases
- Prof. Pierluigi Gambetti
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21. Mitochondrial disorders and neurodegeneration
- Prof. Anthony Schapira
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23. Mutations in parkinsonian syndromes
- Dr. Andrew Singleton
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25. Frontotemporal dementia
- Prof. Bruce Miller
Printable Handouts
Navigable Slide Index
- Intro slide
- The microtubule associated protein tau
- Tau is incorporated into neurofibrillary lesions
- Neurofibrillary pathology in Alzheimer's disease
- The role of A-beta and tau in AD
- Neurodegenerative diseases with tau pathology
- Mutations in tau cause FTDP-17
- Tau mutations in FTDP-17
- Tau mutations effects on tau protein
- Exon 10 splicing mutations
- Tau H1 haplotype is associated with PSP/CBD
- Tau H1 haplotype is associated with PD
- H1 haplotype is linked to higher tau expression
- Genetics of tauopathy - summary
- Tau P301L mice (JNPL3 line)
- Insoluble tau accumulates in P301L mice
- Neuronal loss in tau P301L mice
- Axonal degeneration in P301L mice
- Tau x APP double transgenic mice
- Neurodegeneration in JNPL3 and Tau/APP mice
- Tg4510 an inducible model of tauopathy
- NFT pathology in the Tg4510 mouse
- Progressive deficits in memory in Tg4510
- Design of transgene suppression studies
- Early tau transgene suppression (2.5-4m)
- Tau transgene suppression 4.0M-5.5M
- Insoluble tau species in rTg4510
- TauP301L transgene suppression halts pathology
- Tau transgene suppression improves memory
- Transgene suppression in rTg4510 - summary
- Mechanism of tau induced neurodegeneration
- Acknowledgements - Genetics
- Acknowledgements - Transgenic mice
Topics Covered
- Medical importance of tauopathies
- Microtubule Associated Protein Tau (MAPT) is incorporated into neurofibrillary lesions
- Mutations in the MAPT gene give rise to Frontotemporal dementia with parkinsonism (FTDP-17)
- Common variability in the MAPT, the so-called H1/H1 haplotype and sporadic tauopathies
- Progressive supranuclear Palsy and Cortico-basal degeneration
- Constitutive and conditional transgenic mouse models of tauopathy
- The JNPL3 mouse model of tauopathy
- Neurofibrillary tau pathology in the JNPL3 mice
- A-beta and MAPT pathologies can interact during the development of Alzheimer's disease
- Conditional rTg4510 model of tauopathy
- Major mechanism of neurodegeneration in tauopathy
- Potential therapeutic applications
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Hutton, M. (2022, February 4). The role of MAPT (Tau) in neurodegenerative disease: one bullet with many triggers [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 3, 2024, from https://doi.org/10.69645/QRAX2260.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Michael Hutton has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Update Available
The speaker addresses developments since the publication of the original talk. We recommend listening to the associated update as well as the lecture.
- Full lecture Duration: 51:31 min
- Update interview Duration: 31:40 min
The role of MAPT (Tau) in neurodegenerative disease: one bullet with many triggers
A selection of talks on Clinical Practice
Transcript
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0:00
The role of the microtubule-associated protein tau in neurodegenerative disease.
One bullet with many triggers. The tau protein is
a microtubule-associated protein that plays a role in stabilizing neuronal microtubules.
In addition, it is incorporated into filamentous lesions in a number of
neurodegenerative diseases known collectively as
tauopathy is the most common of which is Alzheimer's disease,
which is the major cause of dementia in the elderly.
In this presentation, I'll describe genetic findings over
the past 10 years that have established
the mechanistic importance of power in neurodegenerative disease.
Then, in the second part of the talk,
I'll describe more recent efforts to generate
transgenic mouse models of these diseases by
expressing tau transgenes in transgenic animals.
0:58
The microtubule-associated protein tau is encoded by
a single gene on chromosome 17 have because it's one,
two, three, and ten are alternatively spliced.
There are six major protein isoforms in the adult human brain.
Exons 9 through 12 encode the microtubule-binding domains within the tower protein.
These are imperfect repeats of 31 and 32 amino acids and
because exon 10 is alternately spliced,
we actually have two major groups of isoforms that contain
three microtubule-binding repeats when exon 10 is spliced out
or four microtubule-binding repeats when exon 10 is spliced in.
These are known usually as three repeat and four repeat tau.
The average isoform ratio of three repeat to four repeat in the normal,
human adult brain is around one to one.
However, it's important to point out that in the fetal brain,
we only see the shortest three repeat isoform and in addition,
in patients with certain types of tau mutation,
they're associated with frontotemporal dementia.
We see a shift in the 3-4 repeat ratio such
that there is a large increase in the level of four repeats to isoforms.
The normal function of the tau protein is to
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